Little research has been done on the prolongation of organ allograft survival by graft pretreatment. In preliminary data, we have shown that (a) plant lectins, ConcanavalinA (ConA) and phytohemagglutinin-M (PHA), bound to mouse lymphoid cells can mask strong histocompatibility antigens; (b) ConA bound to mouse and human lymphoid cells interferes with the alloimmunogenicity of these cells in mixed lymphocyte culture. (c) Most recently we have found that mongrel dog kidneys perfused with ConA in vitro and transplanted into allogeneic dogs, survived for prolonged periods of time. This grant is designed (1) to study the possible mechanisms by which ConA bound to organ grafts can lead to graft prolongation in allogeneic recipients, (2) to determine the optimal conditions for the treatment of organ allografts which will permit prolonged graft survival, (3) to investigate how ConA can alter the immunogenicity of grafts utilizing the mixed lymphocyte culture to simulate immunologic stimulation, (4) to apply the lessons learned with kidney allografts to organ allografts of liver, intestine and heart, and (5) to determine the effects on the immunogenicity of organ and tissue allografts of other substances used to pretreat the graft itself. This work has been pursued now for one year: We have (1) confirmed the essential observation, (2) demonstrated that it is not due to systemically infused ConA, (3) ConA treated kidneys induce systemic hyporeactivity to non-perfused organs, (4) that ConA treated kidneys sensitize non-immunosuppressed animals almost as well as do untreated kidneys, and (5) demonstrated that chondroitin sulphate and dipyridamole, two membrane active drugs, can be utilized in place of ConA in similar type experiments. (6) Finally, we have demonstrated that chlorpromazine and lidocaine in vitro can inhibit membrane interactions between responder and stimulator cells so that such drug membrane interactions may cast light on the mechanism by which the immunogenicity of the cells is decreased by ConA. BIBLIOGRAPHIC REFERENCES: Ferguson, R.M., Schmidtke, J.R., and simmons, R.L.: Inhibition of mitogen-induced lymphocyte transformation by local anesthetics. J. Immunol., 116:627, 1976. Ferguson, R.M., Schmidtke, J.R., and Simmons, R.L.: Differential effects of chlor (Text Truncated - Exceeds Capacity)